TY - JOUR
T1 - Structure Identification and Risk Assurance of Unknown Impurities in Pramipexole Oral Drug Formulation
AU - Tjandrawinata, Raymond R.
AU - Cahyana, Antonius H.
AU - Nugroho, Ajeng O.
AU - Adi, Indra K.
AU - Talpaneni, Joseph S.R.
N1 - Publisher Copyright:
© 2024 Raymond R. Tjandrawinata et al.
PY - 2024
Y1 - 2024
N2 - Impurities compounds in any pharmaceutical product or drug substance are inevitable from a chemistry point of view. The quality and safety of a pharmaceutical product are also significantly affected by these impurities content; therefore, impurities need to be identified and characterized through the use of appropriate analytical methods. Pramipexole is a nonergot dopamine agonist used to treat various Parkinson's disease symptoms. Two unknown impurities were detected from a pramipexole dihydrochloride solid dosage form. These impurities were identified and characterized using ultra-performance liquid chromatography coupled with high-resolution mass spectroscopy (UPLC-HRMS). These impurities were found to be enriched when mannitol existed in the formulation. The structure and mechanism involved in the existence of the impurities were proposed. Furthermore, observation of the binding affinity potential risk of these impurities to the pramipexole receptor has also been demonstrated through molecular docking and molecular dynamics simulation study. The binding energy result showed that pramipexole interaction with dopamine receptors D2 and D3 was higher than pramipexole mannose adduct and pramipexole ribose adduct.
AB - Impurities compounds in any pharmaceutical product or drug substance are inevitable from a chemistry point of view. The quality and safety of a pharmaceutical product are also significantly affected by these impurities content; therefore, impurities need to be identified and characterized through the use of appropriate analytical methods. Pramipexole is a nonergot dopamine agonist used to treat various Parkinson's disease symptoms. Two unknown impurities were detected from a pramipexole dihydrochloride solid dosage form. These impurities were identified and characterized using ultra-performance liquid chromatography coupled with high-resolution mass spectroscopy (UPLC-HRMS). These impurities were found to be enriched when mannitol existed in the formulation. The structure and mechanism involved in the existence of the impurities were proposed. Furthermore, observation of the binding affinity potential risk of these impurities to the pramipexole receptor has also been demonstrated through molecular docking and molecular dynamics simulation study. The binding energy result showed that pramipexole interaction with dopamine receptors D2 and D3 was higher than pramipexole mannose adduct and pramipexole ribose adduct.
UR - http://www.scopus.com/inward/record.url?scp=85186437523&partnerID=8YFLogxK
U2 - 10.1155/2024/5583526
DO - 10.1155/2024/5583526
M3 - Article
AN - SCOPUS:85186437523
SN - 2633-4682
VL - 2024
JO - Advances in Pharmacological and Pharmaceutical Sciences
JF - Advances in Pharmacological and Pharmaceutical Sciences
M1 - 5583526
ER -